The aim of this study was to evaluate the relationship between the serum N-terminal peptide of type III procollagen (PIIINP), Knodell's score and the response to treatment in 79 patients with viral C chronic hepatitis. Liver biopsy and serum PIIINP was assessed in all patients. Serum PIIINP was correlated with Knodell'score (r = 0.60; P = 10(-4)). Correlation between serum alanine amino-transferase and Knodell'score was smaller than for PIIINP (r = 0.38; P = 0.02). Forty-nine patients were treated with interferon alpha. A second biopsy and serum PIIINP determination were performed one year after treatment discontinuation. Means of serum PIIINP and Knodell'score significantly decreased after treatment (P < 0.01; P < 0.03). Among non-responder patients, serum PIIINP was initially more elevated: 37.5 +/- 12.6 ng/mL versus 22.6 +/- 3.8 (P < 10(-3)). Knodell's score decreased only among responder patients (P < 0.01 vs P < 0.7). Positive and negative predictive value for the response to treatment, evaluated by aminotransferases normalization, of serum PIIINP level < or = 24 ng/mL were 0.6 and 0.9 respectively. These findings suggest that serum PIIINP is a relevant marker of activity in patients with viral C chronic hepatitis and that it might have a predictive value of response to treatment.